The neural tube of both avian and mammalian (including human) embryos develops in two distinct phases called primary and secondary neurulation. Primary neurulation has been examined extensively, but secondary neurulation has been studied only sparsely, except in the chicken embryo. The first major goal of this proposed study is to provide important, currently unavailable, information on the morphogenesis of the secondary portion of the neural tube, by characterizing what histological and ultrastructural events constitute secondary neurulation in mammalian embryos, using the mouse embryo as a model system. In addition, because essentially nothing is known about the complex transitional region between primary and secondary neurulation in mammalian embryos, the histology, fine structure, location, and extent of this area will be determined also for the mouse embryo. By these means, our understanding of the events involved in normal formation of the neural tube will be increased, and our comprehension should be enhanced of what may go awry during formation of congenital anomalies of the central nervous system. The second major goal of the proposed study is to determine the origin of neural crest cells, cells destined to give rise to a large number of diverse and important cell types, in areas undergoing secondary neurulation. In cranial and trunk regions, neural crest cells arise from the neural folds, but in caudal regions, the neural folds are absent. The possibility will be tested, therefore, that these cells arise from the tail bud in caudal regions, as does the secondary portion of the neural tube. The origin of neural crest cells of caudal regions will be determined for both mammalian and avian embryos by special staining and ultrastructural techniques, and by the analysis of histological sections of chicken-quail chimeras. With these techniques, it will be possible to answer the question of what is the origin of neural crest cells in areas undergoing secondary neurulation, increasing our knowledge considerably about the sources of these important and fascinating cells.